Tadizolid phosphate has a strong antibacterial activity to pathogens of human and animal, including gram-positive bacteria such as Staphylococcus, Enterococcus and Streptococcus, anaerobic microorganisms such as bacteroid and Clostridium, and acidotolerant microorganisms such as Mycobacterium tuberculosis and Mycobacterium avium complex. Tadizolid (formerly called torezolid) was jointly developed by the Cubist Pharmaceuticals company (a subsidiary of Merck Corporation) and Bayer. It was originally found as an antibacterial drug precursor by Dong-A Pharmaceutical (Dong-A ST) and used for the treatment of gram-positive bacterial infections. Tedizolid is rapidly transformed into its active form TR 700 (DA 7157) in plasma.
WO2005058886A1 discloses the synthesis of 3-[3-fluoro-4-[6-(2-methyl-2H-tetrazol-5-yl)-3-pyridinyl]phenyl]-5-(hydroxymethyl)-2-oxazolidinone, wherein 3-fluoroaniline is used as raw material and reacts with glycidyl butyrate after being protected by Cbz to obtain compound 3. Compound 3 is then iodinated and converted into tin reagent 5, which is Suzuki coupled with 5-bromo-2-(2-methyl-2H-tetrazol-5-yl)-pyridine to produce the key intermediate K. The reaction scheme is depicted as follows:

The reaction procedure of the original drug of Dong-A Pharmaceutical is long, and the total yield is not high. In terms of cost, relatively expensive reagents such as CF3COOAg are needed, and Pd catalyst are needed twice for respectively preparing intermediates 5 and K in the scheme. The reaction conditions are harsh, which is not easy for a large scale production.
Later, the synthetic scheme of the original compound was improved by an licensee Trius Therapeutics company, in whose patent WO2010042887, 4-bromo-3-fluoroaniline is employed as the starting material, first to synthesize boric acid ester 10, which is then Suzuki coupled with 5-bromo-2-(2-methyl-2H-tetrazol-5-yl)-pyridine to generate intermediate 11. Intermediate 11 then reacts with glycidyl butyrate to obtain the oxazolidinone intermediate K. The reaction scheme is depicted as follows:

Compared with the patented method of Dong-A Pharmaceutical, this scheme is short in reaction procedure with an improved total yield. However, the reaction conditions are still rather harsh. Butyl lithium is needed, and the reaction needs to be carried out at ultra-low temperature (−65° C.). The use of n-BuLi and LiHMDS requires strict anhydrous condition.
In addition, CN104496979A discloses a method for preparing tedizolid, which is as depicted in the reaction scheme below:
wherein R is hydrogen or a hydroxyl protective group; one of L and R1 is a leaving group, while the other one is BF3 or BR2R3, wherein R2 and R3 are independently selected from a group consisting of OH, and optionally substituted C1-C6 monohydric alcohol and C1-C6 diol, and wherein R2 and R3 can form a ring. Pd is employed in this scheme to catalyze the synthesis of borate intermediate II. After separation and purification, the intermediate II is Suzuki coupled with compound I under catalysis of Pd to obtain the compound of formula H. In this scheme, the reaction operations are complicated, since the intermediate II needs to be separated out before Suzuki coupling.
The methods of prior art for preparing tedizolid intermediates all suffer from complex operation, long reaction time, low total yield and low purity.